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To investigate whether assisted reproductive technology (ART) affects gross fetal movement. A prospective cohort study. 65 women who conceived with ART (ART group) and 211 women (control group) without ART recorded fetal movement with the fetal movement acceleration measurement recorder at night weekly after 28 weeks. The number ratio of 10 s epochs with fetal movement to all epochs was calculated as the fetal movement parameter. When no fetal movement was observed for more than 5 min, it was defined as a no fetal movement period, and the average number per hour, the average duration, and the longest duration of the no fetal movement periods were calculated as the no fetal movement parameters. Gestational weeks were classified into 28–33 and 34–39 weeks, and the fetal movement parameter and the no fetal movement parameters were compared using the Student's t-test. The fetal movement parameters at 28–33 weeks were 17.43% (ART) and 16.58% (control) (p = 0.219), and those at 34–39 weeks were 11.72% (ART) and 11.96% (control) (p = 0.590). In the same way, for the no fetal movement parameters, the average numbers were 1.58 and 1.63 per hour (p = 0.357), and 2.36 and 2.30 per hour (p = 0.503). The average durations were 8.30 and 8.46 min (p = 0.712), and 9.20 and 9.51 min (p = 0.188). The longest durations were 16.26 and 17.02 min (p = 0.295), and 22.34 and 22.87 min (p = 0.534). ART does not affect gross fetal movement count. [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests that certain fetal anomalies detected upon prenatal ultrasound screenings are associated with autism spectrum disorder (ASD). In this cross-sectional study, we aimed to identify genetic variants associated with fetal ultrasound anomalies (UFAs) in children with ASD. Methods: The study included all children with ASD who are registered in the database of the Azrieli National Center of Autism and Neurodevelopment and for whom both prenatal ultrasound and whole exome sequencing (WES) data were available. We applied our in-house integrative bioinformatics pipeline, AutScore, to these WES data to prioritize rare, gene-disrupting variants (GDVs) probably contributing to ASD susceptibily. Univariate statistics and multivariable regression were used to assess the associations between UFAs and GDVs identified in these children. Results: The study sample comprised 126 children, of whom 43 (34.1%) had at least one UFA detected in the prenatal ultrasound scan. A total of 87 candidate ASD genetic variants were detected in 60 children, with 24 (40%) children carrying multiple variants. Children with UFAs were more likely to have loss-of-function (LoF) mutations (aOR = 2.55, 95%CI: 1.13–5.80). This association was particularly noticeable when children with structural anomalies or children with UFAs in their head and brain scans were compared to children without UFAs (any mutation: aOR = 8.28, 95%CI: 2.29–30.01; LoF: aOR = 5.72, 95%CI: 2.08–15.71 and any mutation: aOR = 6.39, 95%CI: 1.34–30.47; LoF: aOR = 4.50, 95%CI: 1.32–15.35, respectively). GDVs associated with UFAs were enriched in genes highly expressed across all tissues (aOR = 2.76, 95%CI: 1.14–6.68). There was a weak, but significant, correlation between the number of mutations and the number of abnormalities detected in the same children (r = 0.21, P = 0.016). Conclusions: The results provide valuable insights into the potential genetic basis of prenatal organogenesis abnormalities associated with ASD and shed light on the complex interplay between genetic factors and fetal development. [ABSTRACT FROM AUTHOR]

Purpose: To study the effect of decreased estimated fetal weight (EFW) percentiles in appropriate for gestational age fetuses. Methods: This retrospective cohort study included women who had second and third trimester ultrasound examinations. Delivery and neonatal outcomes of pregnancies with decreased EFW of ≥ 30 percentiles in EFW between ultrasound examinations (decreased growth group) and those without such a decrease (control group) were compared. Deliveries with EFW or birthweight below the 10th percentile were excluded. Results: Among 1610 deliveries, 57 were in the decreased growth group and 1553 in the control group. Maternal characteristics did not differ between the groups except for higher rate of nulliparity in the decreased growth group. We found similar rates of Category II/III monitoring, cesarean deliveries due to non-reassuring fetal heart rate and adverse neonatal outcomes. Neonatal birthweight was lower in the decreased growth group as compared to controls. Conclusions: This study did not find association between the group of appropriate for gestational age fetuses with decreased growth, with adverse outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Hyperemesis gravidarum has the potential to affect the long-term health of offspring. We examined whether maternal hyperemesis gravidarum was associated with the risk of hospitalization for childhood morbidity. Methods: We conducted a longitudinal cohort study of 1,189,000 children born in Quebec, Canada, between April 2006 and March 2021. The main exposure measure was maternal hyperemesis gravidarum requiring hospitalization in the first or second trimester. The outcome was any pediatric admission between birth and 16 years of age, with follow-up ending in March 2022. We used Cox regression models adjusted for maternal and socioeconomic factors to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between maternal hyperemesis gravidarum and childhood hospitalization. Results: Among 1,189,000 children, 6904 (0.6%) were exposed to maternal hyperemesis gravidarum. Hospitalization rates at age 16 years were higher for children exposed to hyperemesis gravidarum than unexposed children (47.6 vs 43.9 per 100 children). Relative to no exposure, hyperemesis gravidarum was associated with a 1.21 times greater risk of any hospitalization before 16 years (95% CI 1.17–1.26). Hyperemesis gravidarum was associated with hospitalization for neurologic (HR 1.50, 95% CI 1.32–1.71), developmental (HR 1.51, 95% CI 1.29–1.76), digestive (HR 1.40, 95% CI 1.30–1.52), and allergic disorders (HR 1.39, 95% CI 1.24–1.56). When contrasted with preeclampsia, hyperemesis gravidarum was a stronger risk factor for these outcomes. Conclusions: Maternal hyperemesis gravidarum is associated with an increased risk of childhood hospitalization, especially for neurologic, developmental, digestive, and atopic disorders. What is Known: • Hyperemesis gravidarum is associated with neurodevelopmental disorders in offspring. • However, the effect of hyperemesis gravidarum on other childhood morbidity is unclear. What is New: • In this longitudinal cohort study of 1.2 million children, maternal hyperemesis gravidarum was associated with a greater risk of hospitalization before age 16 years. • Exposure to hyperemesis gravidarum was associated with developmental, neurologic, atopic, and digestive morbidity in childhood. [ABSTRACT FROM AUTHOR]

Purpose: Co-creation of a citizen-science research initiative with a collaborative team of community members and university-based scientists to address regional disparities in maternal and fetal health outcomes for Black birthing people. Description: Citizen scientist-led projects, where community members actively contribute to each discovery step, from setting a research agenda to collecting data and disseminating results, can extend community participatory research initiatives and help reconceptualize traditional research processes. The Pregnancy Collaborative is a citizen-science research initiative and one of nine scientific committees of The Pittsburgh Study—a longitudinal, community-partnered study designed to bring together collaborators to improve child thriving. Assessment: Ten community members and five university-based scientists participated during all phases of developing a citizen-scientist collaboration over an initial two-and-a-half-year period. Phases include forming the Pregnancy Collaborative and group research ethics training; co-creating a research agenda grounded in shared principles; and community-partnered data collection, analysis, and dissemination. These phases produced three key co-designed products: (1) a mission and vision statement of the Pregnancy Collaborative, (2) a Collaborative-endorsed research agenda, and (3) a citizen-scientist-executed research survey. Conclusion: Lessons learned from the formation of the Pregnancy Collaborative highlight the importance of equitable power distribution through bidirectional knowledge sharing and by centering intellectual effort, lived experience, and tools and resources of those affected by health inequities. Using a citizen science approach to co-designing and executing research helps us move maternal health inequity work from "research on" to "research with." Significance: Persistent disparities characterize maternal and child health outcomes in the United States. These disparities, mediated by poverty, racism, and place-based social and structural determinants of health, are the biggest threats to Black maternal health. Recently, community-engaged efforts to improve Black maternal health disparities have moved towards cross-sector approaches that center the lived experiences of Black birthing people. Despite these comprehensive approaches, community members rarely participate throughout the research lifecycle. Citizen science-led projects like those described in this paper are one way to acknowledge and commit to bidirectional community-partnered research and action. [ABSTRACT FROM AUTHOR]

Objective: This study investigates the impact of both maternal psychopathological factors and adaptive psychological changes within the couple on fetal growth, emphasizing the importance of evaluating pregnancy from the perspectives of the couple, the mother, and the fetus collectively. A "couple" in this context refers to heterosexual partners engaged in the pregnancy process together, whether married or in a stable relationship. Methods: We included 189 pregnant women in their first trimester, tracking maternal depression, anxiety, body appreciation, prenatal attachment, and the couple's adjustment level across each trimester. Fetal growth parameters measured include biparietal diameter, femur length, humerus length, abdomen circumference, head circumference, β-HCG, and amniotic fluid levels, with relationships between these variables being modeled accordingly. Results: Our findings indicate stable levels of maternal depression, anxiety, body appreciation, and couple's adjustment throughout the pregnancy, with a significant increase in prenatal attachment levels in each subsequent trimester. Prenatal attachment in the first trimester and maternal depression levels in the second and third trimesters were found to directly influence fetal growth, while other variables exhibited indirect effects. Conclusions: Fetal growth is influenced by a myriad of biopsychosocial factors. Ensuring healthy pregnancy and fetal development necessitates close monitoring and support of the mother's adaptive psychological changes, early identification and treatment of potential psychopathologies, and maintenance of the psychosocial health of the couple. Significance: Although there are studies on the effects of maternal psychopathology on fetal growth, there are few studies that study the effects of adaptive psychological changes during pregnancy and the couple's relationship on fetal growth together with maternal psychopathology. With this study, it was understood that there was only a change in the prenatal attachment levels of the mother during pregnancy, there was no significant change in anxiety, depression, body appreciation and dyadic adjustment, but the mutual interactions of these factors during each trimester had important effects on fetal growth. For a healthy pregnancy and healthy fetal development, it is necessary to closely monitor and support the adaptive psychological changes of the mother, early recognition and appropriate treatment of possible psychopathologies, and the psychosocial health of the couple. [ABSTRACT FROM AUTHOR]

Background: Visualizing (micro)vascular structures remains challenging for researchers and clinicians due to limitations in traditional radiological imaging methods. Exploring the role of vascular development in craniofacial malformations in experimental settings can enhance understanding of these processes, with the effectiveness of high-resolution imaging techniques being crucial for successful research in this field. Micro-CT imaging offers 3D microstructural insights, but requires contrast-enhancing staining agents (CESAs) for visualizing (micro)-vascular tissues, known as contrast-enhanced micro-CT (CECT). As effective contrast agents are crucial for optimal visualization, this review focuses on comparative studies investigating such agents for micro-vascular tissue imaging using micro-CT. Furthermore, we demonstrate the utilization of B-Lugol solution as a promising contrast agent for acquiring high-quality micro-CT images of (micro)vascular structures in human embryonic samples. Method: This scoping review followed Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols. PubMed database provided relevant articles, screened initially by title and abstract. Inclusion and exclusion criteria defined outcomes of interest. Results: From an initial search, 273 records were identified, narrowed down to 9 articles after applying our criteria. Additionally, two articles were added through citation searching. This, a total of 11 articles were incorporated in this study. Conclusion: This micro-CT contrast agent review underscores the need for tailored choices based on research goals. Both Barium sulfate and Iodine-based agents showing excellent results, providing high resolution (micro) vascular content, especially in ex-vivo specimens. However, careful consideration of protocols and tissue characteristics remains imperative for optimizing the effectiveness of micro-CT imaging for the study of cranio-facial vascular development. [ABSTRACT FROM AUTHOR]

The long and very long chain polyunsaturated fatty acids (LC-PUFAs) are preferentially transported by the mother to the fetus. Failure to supply LC-PUFAs is strongly linked with stillbirth, fetal growth restriction, and impaired neurodevelopmental outcomes. However, dietary supplementation during pregnancy is unable to simply reverse these outcomes, suggesting imperfectly understood interactions between dietary fatty acid intake and the molecular mechanisms of maternal supply. Here we employ a comprehensive approach combining untargeted and targeted lipidomics with transcriptional profiling of maternal and fetal tissues in mouse pregnancy. Comparison of wild-type mice with genetic models of impaired lipid metabolism allows us to describe maternal hepatic adaptations required to provide LC-PUFAs to the developing fetus. A late pregnancy-specific, selective activation of the Liver X Receptor signalling pathway dramatically increases maternal supply of LC-PUFAs within circulating phospholipids. Crucially, genetic ablation of this pathway in the mother reduces LC-PUFA accumulation by the fetus, specifically of docosahexaenoic acid (DHA), a critical nutrient for brain development. Fetal brain development is dependent on the maternal supply of long chain polyunsaturated fatty acids (LC-PUFAs). Here, the authors show that pregnancy-induced liver-X-receptor (LXR) signaling in the maternal liver promotes the synthesis of LC-PUFA-containing phospholipids for export to the fetus. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review aimed to determine the effects of maternal exposure to bisphosphonates (BPs) during pregnancy on neonatal outcomes. It aimed to disclosfe the impact of BPs on neonates and identify aspects that require further investigation. Methods: A comprehensive search of PubMed, Science Direct, LILACS, EMBASE, and Web of Science was conducted until August 2022, with no time restrictions. The selection criteria included studies published in English that evaluated pregnant women who were exposed to BPs. Results: From an initial pool of 2169 studies, 13 met the inclusion criteria for this systematic review. These studies collectively included 106 women (108 pregnancies) who were exposed to BPs either before orduring pregnancy. A summary of the key characteristics of the selected studies and the risk of bias assessment are provided. Exposure to BPs occurs at various stages of pregnancy, with different indications for BP treatment. The most frequently reported neonatal outcomes were spontaneous abortion, congenital malformations, hypocalcemia, preterm birth, and low birth weight. Conclusion: Although previous reports have linked BPs before or during pregnancy with adverse neonatal outcomes, these associations should be interpreted with caution. Given the complexity of these findings, further research is necessary to provide more definitive insights to guide clinical decisions regarding the use of BPs in pregnant women. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that gestational diabetes mellitus (GDM) alters the growth trajectory of a fetus and increases the risk of abnormal birth weight. In spite of this, there is still a significant debate regarding the mode and optimal timing of diagnosing this condition. Our aim was to determine fetal growth velocity and birth biometry in pregnant women with GDM at varying risk levels. Methods: We conducted a cohort study involving 1023 pregnant women at a maternity hospital in Ma'anshan, China. All women completed an oral glucose tolerance test at 24–28 weeks' gestation. We measured fetal head circumference (HC), femoral length (FL), abdominal circumference (AC), biparietal diameter (BPD), and estimate fetal weight (EFW) by ultrasound at 17, 24, 31, and 35 weeks' gestation, respectively. Results: Overall, 5115 ultrasound scans were performed. Among both low-risk and medium–high-risk pregnant women at 17–24 weeks' gestation, GDM exposure was associated with an increase in fetal growth velocity. Neonates born to women with GDM at medium–high risk had significantly larger birth weights than those born to women without GDM, while this was not observed in women at low risk. Conclusion: In medium–high-risk pregnant women, exposure to GDM has a greater effect on the fetus, leading to abnormal fetal growth velocity that lasts beyond week 24. It is evident from our results that the effects of GDM on fetal growth differ between medium–high-risk pregnant women and low-risk pregnant women, and therefore a different screening program based on the risk factor for GDM is warranted. [ABSTRACT FROM AUTHOR]

Purpose: Maternal cortisol levels in pregnancy may support the growth of or adversely affect fetal organs, including the brain. While moderate cortisol levels are essential for fetal development, excessive or prolonged elevations may have negative health consequences for both the mother and the offspring. Little is known about predictors of altered hypothalamic–pituitary–adrenal (HPA) axis activity during pregnancy. This study examined maternal hair cortisol concentration (HCC) in the 3rd trimester of pregnancy in relation to severe psychopathology. Methods: Hair samples were collected from 69 women, 32 with a lifetime diagnosis of severe mental disorders (bipolar I or II disorder, moderate or severe depressive disorder, schizophrenic spectrum disorder), and 37 non-clinical controls. Hair samples were collected during the 3rd trimester, and liquid chromatography tandem mass spectrometry was used for cortisol assessment. Psychiatric diagnosis and current level of symptomatic functioning were assessed using the structured clinical interview from the DSM-5 and the global assessment of functioning scale. Results: Women with a lifetime diagnosis of severe mental illness had significantly elevated HCC compared to controls. Poorer current symptomatic functioning was also significantly associated with elevated HCC in pregnancy. Conclusions: The implications of alterations in HCC on both maternal and infant health need further study. [ABSTRACT FROM AUTHOR]

Branchial arch anomalies are considered congenital defects that can occur during fetal development. They may present as cysts, sinuses, or fistulae. Anomalies of the second branchial arch are the most common. The existence of bilateral complete fistulae is exceptionally rare. In this case report, a 5-year-old boy presented with recurrent episodes of bilateral neck swelling and watery discharge from openings on the anterolateral sides of his neck since birth. He was diagnosed with bilateral branchial fistulae after confirmation via a contrast-enhanced CT scan. Surgery was performed to entirely excise the fistula tracts bilaterally. Additionally, a bilateral tonsillectomy was performed to help prevent recurrence. [ABSTRACT FROM AUTHOR]

Abstract—Fetal growth restriction is a complication of pregnancy that is defined as the inability of the fetus to realize its genetically determined growth potential. Despite the high social and medical significance of this problem the exact pathogenesis of fetal growth restriction is not known. Therefore, the analysis of the molecular genetics mechanisms of this pathology within the framework of approaches using modern high-performance technologies of next generation sequencing is of undoubted interest. In this review we focused on the analysis of data obtained in studies of the genetics component of fetal growth restriction. The authors of these studies used next generation sequencing technologies and carried out whole transcriptome profiling. The results of the gene expression genome-wide analysis in placental tissue allow us to identify 1430 differentially expressed genes between fetal growth restriction and normal pregnancy, of which only 1% were found in at least two studies. These differentially expressed genes are involved in the Wnt/β-catenin signaling pathway, which plays an important role in cell migration, neural pattern formation and organogenesis during embryonic development. Common genes are associated with both obstetric and gynecological diseases, as well as with various somatic conditions from the groups of neurodegenerative, cardiovascular diseases and mental disorders, which probably reflects their involvement in the development of postnatal consequences of fetal growth restriction. The results of our work do not only point to potential molecular mechanisms and key genes underlying fetal growth restriction, but also indicate the important role of gene–gene communications in this pathology: about 30% of all identified differentially expressed genes products interact with each other within the same gene network. In general, genome-wide RNA sequencing combined with the analysis of protein–protein interactions represents a promising direction in research in the development and functioning of the placenta, as well as the identification of genetic mechanisms of placental insufficiency diseases, including fetal growth restriction. [ABSTRACT FROM AUTHOR]

The placenta is crucial for fetal development, yet the impact of environmental stressors such as arsenic exposure remains poorly understood. We apply single-cell RNA sequencing to analyze the response of the mouse placenta to arsenic, revealing cell-type-specific gene expression, function, and pathological changes. Notably, the Prap1 gene, which encodes proline-rich acidic protein 1 (PRAP1), is significantly upregulated in 26 placental cell types including various trophoblast cells. Our study shows a female-biased increase in PRAP1 in response to arsenic and localizes it in the placenta. In vitro and ex vivo experiments confirm PRAP1 upregulation following arsenic treatment and demonstrate that recombinant PRAP1 protein reduces arsenic-induced cytotoxicity and downregulates cell cycle pathways in human trophoblast cells. Moreover, PRAP1 knockdown differentially affects cell cycle processes, proliferation, and cell death depending on the presence of arsenic. Our findings provide insights into the placental response to environmental stress, offering potential preventative and therapeutic approaches for environment-related adverse outcomes in mothers and children. Environmental stressors have been associated with placental dysfunction and pregnancy complications. Here, the authors reveal gene expression changes in the mouse placenta exposed to arsenic at single-cell resolution and identify a potential therapeutic target to mitigate its harmful effects on pregnancy and fetal development. [ABSTRACT FROM AUTHOR]

Methadone is a synthetic long-acting opioid that is increasingly used in the replacement therapy of opioid-addicted patients, including pregnant women. However, methadone therapy in this population poses challenges, as it induces cognitive and behavioral impairments in infants exposed to this opioid during prenatal development. In animal models, prenatal methadone exposure results in detrimental consequences to the central nervous system, such as: (i) increased neuronal apoptosis; (ii) disruption of oligodendrocyte maturation and increased apoptosis and (iii) increased microglia and astrocyte activation. However, it remains unclear whether these deleterious effects result from a direct effect of methadone on brain cells. Therefore, our goal was to uncover the impact of methadone on single brain cell types in vitro. Primary cultures of rat neurons, oligodendrocytes, microglia, and astrocytes were treated for three days with 10 µM methadone to emulate a chronic administration. Apoptotic neurons were identified by cleaved caspase-3 detection, and synaptic density was assessed by the juxtaposition of presynaptic and postsynaptic markers. Apoptosis of oligodendrocyte precursors was determined by cleaved caspase-3 detection. Oligodendrocyte myelination was assessed by immunofluorescence, while microglia and astrocyte proinflammatory activation were assessed by both immunofluorescence and RT-qPCR. Methadone treatment increased neuronal apoptosis and reduced synaptic density. Furthermore, it led to increased oligodendrocyte apoptosis and a reduction in the myelinating capacity of these cells, and promoted the proinflammatory activation of microglia and astrocytes. We showed that methadone, the most widely used drug in opioid replacement therapy for pregnant women with opioid addiction, directly impairs brain cells in vitro, highlighting the need for developing alternative therapies to address opioid addiction in this population. [ABSTRACT FROM AUTHOR]

In a previous Space Shuttle/Spacelab experiment (STS-42), we observed direct responses of isolated fetal mouse long bones to near weightlessness. This paper aimed to verify those results and study the effects of daily 1×g exposure during microgravity on the growth and mineralization of these bones. Two experiments were conducted: one on an American Space Shuttle mission (IML-2 on STS-65) and another on a Russian Bio-Cosmos flight (Bion-10 on Cosmos-2229). Despite differences in hardware, both used 17-day-old fetal mouse metatarsals cultured for 4 days. Results showed reduced proteoglycan content under microgravity compared to 1×g conditions, with no main differences in other cellular structures. While the overall metatarsal length was unaffected, the length increase of the mineralized diaphysis was significantly reduced under microgravity. Daily 1×g exposure for at least 6 h abolished the microgravity-induced reduction in cartilage mineralization, indicating the need for long-duration exposure to 1×g as an in-flight countermeasure using artificial gravity. [ABSTRACT FROM AUTHOR]

Background: Glucokinase-maturity onset diabetes of the young (GCK-MODY) is a form of monogenic diabetes that is caused by heterozygous inactivating mutations in GCK gene. The management of GCK-MODY during pregnancy is challenging, as pharmacological treatment dose could not alter glycaemia in GCK-MODY in longitudinal studies and noninvasive antenatal fetal GCK genotyping is unavailable. Case presentation: Here, we report a case of GCK-MODY with pregnancy. The patient was 41 years old. She was diagnosed with GCK-MODY at 10 weeks of gestation. At 22 weeks and 6 days of gestation, she underwent amniocentesis due to her advanced age and genetic testing confirmed that the fetus was a heterozygous mutation carrier. We described the characteristics of blood glucose fluctuation, insulin responsiveness, hypoglycemic risk, fetal development, and pregnancy outcome before and after fetus genetic testing during her entire pregnancy. Until now, there were no studies describing insulin titration and blood glucose fluctuations during pregnancy in patients with GCK-MODY. Conclusion: Our case indicted that insulin therapy during pregnancy is effective in GCK-MODY. Careful dietary modifications, individualized insulin titration and specialized diabetes education can reduce the risk of hypoglycemia and improve gestational outcome in GCK-MODY with pregnancy. [ABSTRACT FROM AUTHOR]

Activation of the maternal immune system during gestation has been associated with an increased risk for neurodevelopmental disorders in the offspring, particularly schizophrenia and autism spectrum disorder. Microglia, the tissue-resident macrophages of the central nervous system, are implicated as potential mediators of this increased risk. Early in development, microglia start populating the embryonic central nervous system and in addition to their traditional role as immune responders under homeostatic conditions, microglia are also intricately involved in various early neurodevelopmental processes. The timing of immune activation may interfere with microglia functioning during early neurodevelopment, potentially leading to long-term consequences in postnatal life. In this review we will discuss the involvement of microglia in brain development during the prenatal and early postnatal stages of life, while also examining the effects of maternal immune activation on microglia and neurodevelopmental processes. Additionally, we discuss recent single cell RNA-sequencing studies focusing on microglia during prenatal development, and hypothesize how early life microglial priming, potentially through epigenetic reprogramming, may be related to neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

Spontaneous previable rupture of membranes complicates approximately 0.4–0.7% of pregnancies and is associated with severe maternal and neonatal morbidity and mortality. Intra-amniotic inflammation is present in up to 94.4% of cases, most often caused by a bacterial infection. In comparison, the effectiveness of antibiotic therapy in its eradication reaches less than 17%. Inflammatory activity in the amniotic cavity disrupts the physiological development of the fetus with an increase in maternal, fetal, and neonatal inflammatory morbidity through the development of fetal inflammatory response syndrome, maternal chorioamnionitis, and neonatal sepsis. Amniopatch is an invasive therapeutic technique based on intra-amniotic administration of maternal hemoderivates in the form of thromboconcentrate and plasma cryoprecipitate to provide the temporary closure of the fetal membranes defect and secondary restitution of normohydramnios with correction of pressure–volume ratios. The supposed basis of this physical–mechanical action is the aggregation of coagulant components of amniopatch in the area of the defect with the formation of a valve cap. The background for the formulation of the hypothesis on the potential anti-infectious and anti-inflammatory action of non-coagulant components of amniopatch involved: i) clinical–academic and publishing outputs of the authors based on their many years' experience with amniopatch application in the treatment of spontaneous previable rupture of membranes (2008–2019), ii) the documented absence of clinically manifested chorioamnionitis in patients treated this way with a simultaneously reduced incidence of neonatal respiratory distress syndrome compared to expectant management (tocolysis, corticotherapy, antibiotic therapy). The non-coagulant components of plasma cryoprecipitate include mainly naturally occurring isohemagglutinins, albumin, and soluble plasma fibrinogen. Although these components of the amniopatch have not been attributed a significant therapeutic role, the authors assume that due to their opsonizing and aggregative properties, they can significantly participate in optimizing the intrauterine environment through the reduction in bacterial and cytokine charge in the amniotic fluid. The authors think these facts constitute a vital stimulus to future research–academic activity and, at the same time, an idea for reconsidering the therapeutic role of amniopatch as a tool for improving perinatal results of spontaneous previable ruptures of membranes. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of obesity on fetal cortical development. Methods: This prospective cross-sectional study was conducted with 91 pregnant women. Fetal neurosonography scans were performed in the third trimester, and according to body mass index (BMI) values, the patients were evaluated in two groups: obese (BMI ≥ 30 kg/m2) and normal weight (BMI < 30 kg/m2). During neurosonography, fetal insular depth and Sylvian fissures, parieo-occipital and cingulate fissure depth, frontal lobe length, and the sizes of the corpus callosum and cavum septum pellucidum were measured using a transvaginal approach. Fetal cortical development and Sylvian fissure operculization were graded. Results: The number of patients with grade 2 fetal cortical development was significantly higher among the pregnant women in the obese group compared to the normal weight group (n = 17, 41.5% and n = 8, 16.0%, respectively; p = 0.007). In the obese group, the number of pregnant women with grade 4 or below fetal Sylvian fissure operculization was significantly higher (n = 13, 31.7%), and the number of those with grade 9 or above operculization was significantly lower (n = 1, 2.5%) (p = 0.003). The fetal insular depth, frontal lobe anterior–posterior diameter, cingulate fissure depth, and corpus callosum thickness were lower in the obese group, albeit with no significant difference. Parieto-occipital depth significantly decreased in the obese group [6.8 (6) mm)] compared to the control group [10.5 (7.2) mm)] (p = 0.008). The fetal Sylvian fissure ratio and the cavum septum pellucidum ratio were found to be similar between the groups. Conclusion: The data obtained from this study showed that obesity caused fetal cortical changes in pregnant women. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association of parity with a range of neonatal anthropometric measurements in a cohort of uncomplicated term singleton pregnancies. Methods: Retrospective cohort study of patients with a singleton term birth at a single tertiary center (2014–2020) was carried out. The primary exposure was parity. The following neonatal anthropometric measures were considered: birthweight, head circumference, length, ponderal index, and neonatal body mass index (BMI). Results: A total of 8134 patients met the study criteria, 1949 (24.0%) of whom were nulliparous. Compared with multiparous patients, infants of nulliparous patients had a lower mean percentile for birthweight (43.1 ± 26.4 vs. 48.3 ± 26.8 percentile, p < 0.001), head circumference (44.3 ± 26.4 vs. 48.1 ± 25.5 percentile, p < 0.001), length (52.6 ± 25.1 vs. 55.5 ± 24.6 percentile, p < 0.001), ponderal index (34.4 ± 24.0 vs. 37.6 ± 24.2 percentile, p < 0.001), and BMI (39.1 ± 27.1 vs. 43.9 ± 27.3 percentile, p < 0.001). In addition, infants of nulliparous patients had higher odds of having a small (< 10th percentile for gestational age) birthweight (aOR 1.32 [95% CI 1.12–1.56]), head circumference (aOR 1.54 [95% CI 1.29–1.84]), length (aOR 1.50 [95% CI 1.16–1.94]), ponderal index (aOR 1.30 [95% CI 1.12–1.51]), and body mass index (aOR 1.42 [95% CI 1.22–1.65]). Most neonatal anthropometric measures increased with parity until a parity of 2, where it seemed to reach a plateau. Conclusion: Parity has an independent impact on a wide range of neonatal anthropometric measures, suggesting that parity is associated with both fetal skeletal growth and body composition. In addition, the association of parity with fetal growth does not follow a continuous relationship but instead reaches a plateau after the second pregnancy. [ABSTRACT FROM AUTHOR]

New human life begins in the uterus in a period of both extreme plasticity and sensitivity to environmental disturbances. The fetal stage is also a vital period for central nervous system development, with experiences at this point profoundly and permanently shaping brain structure and function. As such, some brain disorders may originate in utero. Glucocorticoids, a class of essential stress hormones, play indispensable roles in fetal development, but overexposure may have lasting impacts on the brain. In this review, we summarize data from recent clinical and non-clinical studies regarding alterations in fetal brains due to prenatal glucocorticoid overexposure that are associated with nervous system disorders. We discuss relevant changes to brain structure and cellular functions and explore the underlying molecular mechanisms. In addition, we summarize factors that may cause differential outcomes between varying brain regions, and outline clinically feasible intervention strategies that are expected to minimize negative consequences arising from fetal glucocorticoid overexposure. Finally, we highlight the need for experimental evidence aided by new technologies to clearly determine the effects of excessive prenatal glucocorticoid exposure. This review consolidates diverse findings to help researchers better understand the relationship between the prenatal glucocorticoid overexposure and the effects it has on various fetal brain regions, promoting further development of critical intervention strategies. [ABSTRACT FROM AUTHOR]

In the recent years, zinc oxide nanoparticles (ZnO NPs) exhibit attractive attention due to their special physical and chemical properties. With the wide applications of ZnO NPs in nanoproducts, the potential risk increased more concerns. Previous studies have revealed that ZnO NPs induced oxidative stress and eventually the cancer process. However, critical knowledge on the adverse effects of ZnO NPs was associated with fetal toxicity. Here, we conducted a systematic investigation to observe the ZnO NP-induced reproductive and developmental toxicity and explore the potential toxic mechanisms. Based on the vital role of Wnt pathway in embryonic development, we supposed that Wnt/β-catenin pathway might contribute to ZnO NP-induced fetal toxicity. After oral administration of ZnO NPs (100 and 200 mg/kg) and ZnCl2 (20 mg/kg) for 14 consecutive days by gavage, we observed ZnO NP-accumulation in maternal and fetal organs as well as fetal growth and development. Meanwhile, we also observed several protein expressions related to the Wnt pathway. We found that after crossing the placental barrier, ZnO NPs accumulated in the fetal liver and induced fetal malformations. Furthermore, the protein expressions of clathrin, caveolae, Wnt-1, and β-catenin were dose-dependent increase. These results demonstrated that ZnO NPs might cross the placental barrier via clathrin and caveolae-mediated endocytosis. In addition, the activation of Wnt/β-catenin pathway might play a role in ZnO NPs inducing fetal growth restriction and malformations. Overall, our study provided a basic understanding of the reproductive toxicity of ZnO NPs to pregnant mice and indicated that the pregnancy was vulnerable to nanotoxicity. [ABSTRACT FROM AUTHOR]

Purpose: To describe fetal brain Magnetic Resonance Imaging (MRI) findings in a large series of monochorionic (MC) pregnancies complicated by Twin Anemia-Polycythemia Sequence (TAPS) prenatally diagnosed, so to characterize the potential intracranial complications associated with this condition, their frequency and potential treatment options. Methods: This is a retrospective study of MC twin pregnancies complicated by TAPS and undergone fetal MRI in a single institution from 2006 to 2023. MRI control was performed and post-natal ultrasound (US) or MRI were available. Results: 1250 MC pregnancies were evaluated in our institution. 50 pregnancies (4%) were diagnosed with TAPS, 29 underwent a fetal brain MRI. 13/29 pregnancies (44.8%) demonstrated brain findings at MRI in at least a twin. Neuroradiological findings were detected in 14/57 twins (24.6%). We detected four main categories of findings: hemorrhagic lesions, T2-weighted white-matter hyperintensities (WMH), brain edema-swelling and venous congestion. Nineteen findings were present in the anemic and three in the polycythemic twins, with a statistically significant ratio between the two groups (p-value = 0.01). Intrauterine MRI follow-up demonstrated the sequalae of hemorrhagic lesions. A complete regression of brain swelling, veins prominence and T2-WMHs was demonstrated after treatment. Postnatal imaging confirmed prenatal features. Conclusions: Our work demonstrates that TAPS-related MRI anomalies consisted in edematous/hemorrhagic lesions that occur mostly in anemic rather than in polycythemic twins. Fetoscopic laser surgery could have a potential decongestant role. Therefore, prenatal MRI may help in counselling and management in TAPS pregnancies, especially for the planning of therapy and the monitoring of its efficacy. [ABSTRACT FROM AUTHOR]

Background: Minor physical anomalies (MPAs) are congenital morphological abnormalities linked to disruptions of fetal development. MPAs are common in 22q11.2 deletion syndrome (22q11DS) and psychosis spectrum disorders (PS) and likely represent a disruption of early embryologic development that may help identify overlapping mechanisms linked to psychosis in these disorders. Methods: Here, 2D digital photographs were collected from 22q11DS (n = 150), PS (n = 55), and typically developing (TD; n = 93) individuals. Photographs were analyzed using two computer-vision techniques: (1) DeepGestalt algorithm (Face2Gene (F2G)) technology to identify the presence of genetically mediated facial disorders, and (2) Emotrics—a semi-automated machine learning technique that localizes and measures facial features. Results: F2G reliably identified patients with 22q11DS; faces of PS patients were matched to several genetic conditions including FragileX and 22q11DS. PCA-derived factor loadings of all F2G scores indicated unique and overlapping facial patterns that were related to both 22q11DS and PS. Regional facial measurements of the eyes and nose were smaller in 22q11DS as compared to TD, while PS showed intermediate measurements. Conclusions: The extent to which craniofacial dysmorphology 22q11DS and PS overlapping and evident before the impairment or distress of sub-psychotic symptoms may allow us to identify at-risk youths more reliably and at an earlier stage of development. [ABSTRACT FROM AUTHOR]

The fetal development of organs and functions is vulnerable to perturbation by maternal inflammation which may increase susceptibility to disorders after birth. Because it is not well understood how the placenta and fetus respond to acute lung- inflammation, we characterize the response to maternal pulmonary lipopolysaccharide exposure across 24 h in maternal and fetal organs using multi-omics, imaging and integrative analyses. Unlike maternal organs, which mount strong inflammatory immune responses, the placenta upregulates immuno-modulatory genes, in particular the IL-6 signaling suppressor Socs3. Similarly, we observe no immune response in the fetal liver, which instead displays metabolic changes, including increases in lipids containing docosahexaenoic acid, crucial for fetal brain development. The maternal liver and plasma display similar metabolic alterations, potentially increasing bioavailability of docosahexaenoic acid for the mother and fetus. Thus, our integrated temporal analysis shows that systemic inflammation in the mother leads to a metabolic perturbation in the fetus. Maternal immune activation during pregnancy can negatively impact the developing fetus. Here, applying multi-omics (RNA-seq, phosphoproteomics and lipidomics) and imaging, the authors show that while maternal immune activation induces strong innate response in maternal organs it does not extend through the placenta but leads to fetal metabolic changes. [ABSTRACT FROM AUTHOR]

Placental leptin may impact foetal development. Maternal overnutrition has been linked to increased plasma leptin levels and adverse effects on offspring, whereas choline, an essential nutrient for foetal development, has shown promise in mitigating some negative impacts of maternal obesity. Here, we investigate whether a maternal obesogenic diet alters foetal growth and leptin levels in the foetal stomach, amniotic fluid (AF), and placenta in late gestation and explore the potential modulating effects of maternal choline supplementation. Female rats were fed a control (CD) or a western diet (WD) four weeks before mating and during gestation, half of them supplemented with choline (pregnancy days 11–17). Leptin levels (in foetal stomach, AF, and placenta) and leptin gene expression (in placenta) were assessed on gestation days 20 and 21. At day 20, maternal WD feeding resulted in greater leptin levels in foetal stomach, placenta, and AF. The increased AF leptin levels were associated with a premature increase in foetal weight in both sexes. Maternal choline supplementation partially prevented these alterations, but effects differed in CD dams, causing increased AF leptin levels and greater weight in male foetuses at day 20. Maternal choline supplementation effectively mitigates premature foetal overgrowth induced by an obesogenic diet, potentially linked to increased AF leptin levels. Further research is needed to explore the sex-specific effects. [ABSTRACT FROM AUTHOR]

Human adolescent and adult skeletons exhibit sexual dimorphism in the pelvis. However, the degree of sexual dimorphism of the human pelvis during prenatal development remains unclear. Here, we performed high-resolution magnetic resonance imaging-assisted pelvimetry on 72 human fetuses (males [M]: females [F], 34:38; 21 sites) with crown-rump lengths (CRL) of 50–225 mm (the onset of primary ossification). We used multiple regression analysis to examine sexual dimorphism with CRL as a covariate. Females exhibit significantly smaller pelvic inlet anteroposterior diameters (least squares mean, [F] 8.4 mm vs. [M] 8.8 mm, P = 0.036), larger subpubic angle ([F] 68.1° vs. [M] 64.0°, P = 0.034), and larger distance between the ischial spines relative to the transverse diameters of the greater pelvis than males. Furthermore, the sacral measurements indicate significant sex-CRL interactions. Our study suggests that sexual dimorphism of the human fetal pelvis is already apparent at the onset of primary ossification. Pelvimetry and regression analysis show sexual dimorphism in the human fetal pelvis during primary ossification at pelvic inlet, subpubic angle, and the ischial spines' distance to the transverse diameter of greater pelvis ratio. [ABSTRACT FROM AUTHOR]

Purpose: The common marmoset (Callithrix jacchus) provides an ideal model to study early development of primates, and an in vivo platform to validate conclusions from in vitro studies of human embryos and embryo models. Currently, however, no established staging atlas of marmoset embryonic development exists. Using high-resolution, longitudinal ultrasound scans on live pregnant marmosets, we present the first dynamic in vivo imaging of entire primate gestation beginning with attachment until the last day before birth. Methods: Our study unveils the first dynamic images of an in vivo attached mammalian embryo developing in utero, and the intricacies of the delayed development period unique to the common marmoset amongst primates, revealing a window for somatic interventions. Results: Established obstetric and embryologic measurements for each scan were used comparatively with the standardized Carnegie staging of human development to highlight similarities and differences. Our study also allows for tracking the development of major organs. We focus on the ontogeny of the primate heart and brain. Finally, input ultrasound images were used to train deep neural networks to accurately determine the gestational age. All our ultrasounds and staging data recording are posted online so that the atlas can be used as a community resource toward monitoring and managing marmoset breeding colonies. Conclusion: The temporal and spatial resolution of ultrasound achieved in this study demonstrates the promise of noninvasive imaging in the marmoset for the in vivo study of primate-specific aspects of embryonic and fetal development. [ABSTRACT FROM AUTHOR]

Background: Pituitary gland height reflects secretory activity of the hypothalamo-pituitary axis. Objective: To assess the cumulative impact of fetal growth and sex on pituitary gland height in premature twins, dissociated from prematurity. Materials and Methods: A retrospective study was conducted, assessing the pituitary gland height in 63 pairs of preterm twins, measured from T1-weighted magnetic resonance imaging (MRI). Auxological parameters, including body weight, body length, and head circumference, at birth and at the time of MRI, were used as proxies for fetal and postnatal growth, respectively. The study population was divided into two groups, using corrected age at around term equivalent as the cutoff point. Statistical analysis was performed using mixed-effects linear regression models. Results: When pituitary gland height was evaluated at around term equivalent, a greater pituitary gland height, suggesting a more immature hypothamo-pituitary axis, was associated with the twin exhibiting lower auxological data at birth. The same association was observed when body weight and length at MRI were used as covariants. In the group evaluated after term equivalent, a smaller pituitary gland height, suggesting a more mature hypothamo-pituitary axis, was associated with male sex. This difference was observed in twin pairs with higher average body weight at birth, and in babies exhibiting higher auxological data at MRI. Conclusion: After isolating the effect of prematurity, at around term equivalent, pituitary gland height reflects the cumulative impact of fetal growth on the hypothalamo-pituitary axis. Subsequently, pituitary gland height shows effects of sex and of fetal and postnatal growth. [ABSTRACT FROM AUTHOR]

The juxtaposition of two seemingly disparate physiological phenomena within the human body—namely, cancer and pregnancy—may offer profound insights into the intricate interplay between malignancies and the immune system. Recent investigations have unveiled striking similarities between the pivotal processes underpinning fetal implantation and successful gestation and those governing tumor initiation and progression. Notably, a confluence of features has emerged, underscoring parallels between the microenvironment of tumors and the maternal–fetal interface. These shared attributes encompass establishing vascular networks, cellular mobilization, recruitment of auxiliary tissue components to facilitate continued growth, and, most significantly, the orchestration of immune-suppressive mechanisms. Our particular focus herein centers on the phenomenon of immune suppression and its protective utility in both of these contexts. In the context of pregnancy, immune suppression assumes a paramount role in shielding the semi-allogeneic fetus from the potentially hostile immune responses of the maternal host. In stark contrast, in the milieu of cancer, this very same immunological suppression fosters the transformation of the tumor microenvironment into a sanctuary personalized for the neoplastic cells. Thus, the striking parallels between the immunosuppressive strategies deployed during pregnancy and those co-opted by malignancies offer a tantalizing reservoir of insights. These insights promise to inform novel avenues in the realm of cancer immunotherapy. By harnessing our understanding of the immunological events that detrimentally impact fetal development, a knowledge grounded in the context of conditions such as preeclampsia or miscarriage, we may uncover innovative immunotherapeutic strategies to combat cancer. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the pulmonary vasculature in baseline conditions and after maternal hyperoxygenation in growth restricted fetuses (FGR). A prospective cohort study of singleton pregnancies including 97 FGR and 111 normally grown fetuses was carried out. Ultrasound Doppler of the pulmonary vessels was obtained at 24–37 weeks of gestation and data were acquired before and after oxygen administration. After, Machine Learning (ML) and a computational model were used on the Doppler waveforms to classify individuals and estimate pulmonary vascular resistance (PVR). Our results showed lower mean velocity time integral (VTI) in the main pulmonary and intrapulmonary arteries in baseline conditions in FGR individuals. Delta changes of the main pulmonary artery VTI and intrapulmonary artery pulsatility index before and after hyperoxygenation were significantly greater in FGR when compared with controls. Also, ML identified two clusters: A (including 66% controls and 34% FGR) with similar Doppler traces over time and B (including 33% controls and 67% FGR) with changes after hyperoxygenation. The computational model estimated the ratio of PVR before and after maternal hyperoxygenation which was closer to 1 in cluster A (cluster A 0.98 ± 0.33 vs cluster B 0.78 ± 0.28, p = 0.0156). Doppler ultrasound allows the detection of significant changes in pulmonary vasculature in most FGR at baseline, and distinct responses to hyperoxygenation. Future studies are warranted to assess its potential applicability in the clinical management of FGR. [ABSTRACT FROM AUTHOR]

Purpose: Although small for gestational age (SGA) does not cause adverse perinatal outcomes, the placental pathology for fetal growth restricted (FGR) and SGA fetuses is still unknown. The aim of this study is to evaluate the differences between placentas of early onset FGR, late onset FGR, SGA, and appropriate for gestational age (AGA) pregnancies in the manner of microvasculature and expression of anti-angiogenic PEDF factor and CD68. Methods: The study included four groups (early onset FGR, late onset FGR, SGA and AGA). Placental samples were obtained just after labor in all of the groups. Degenerative criteria were investigated with Hematoxylin–eosin staining. Immunohistochemical evaluation with H score and m RNA levels of Cluster of differentiation 68 (CD68) and pigment epithelium derived factor (PEDF) were performed for each group. Results: The highest levels of degeneration were detected in the early onset FGR group. In means of degeneration SGA placentas were found to be worse than the AGA placentas. The intensity of PEDF and CD68 were significant in early FGR, the late FGR and SGA groups compared to the AGA group (p < 0.001). The mRNA level results of the PEDF and CD68 were also parallel to the immunostaining results. Conclusion: Although SGA fetuses are considered constitutionally small, the SGA placentas also demonstrated signs of degeneration similar to the FGR placentas. These degenerative signs were not seen among the AGA placentas. [ABSTRACT FROM AUTHOR]

Background: There is currently no information on positional changes in the brachial nerve plexus during prenatal growth. The subclavian–axillary artery passing through the medianus nerve ansa is considered a good landmark for evaluating the height of the plexus. Materials and methods: We used histologic sections from 9 embryos and 17 fetuses (approximately 6–15 weeks of gestational age) to identify the height of the ansa by referring to the level of the rib and the glenohumeral joint. Results: The nerve ansa was usually (23 plexuses) observed at the level of the first and/or second ribs. However, it was sometimes observed above the first rib, at a distance equal to or more than an intercostal width (7 plexuses). In the latter group, the ansa was usually located below the glenohumeral joint. Thus, the joint was located higher than the first rib, although the upper extremities were in the anatomic position for all specimens. The left–right difference in the height of the plexus corresponded to or was less than the width of the first intercostal space. Despite the synchronized growth between the thorax and shoulder girdle, the brachial plexus showed a considerable variation in comparative height; the range corresponded to twice of an intercostal width. Whether the nerve plexus is located high or low is determined at an early developmental stage and is maintained during the later growth stages. Conclusion: The high-positioned plexus might cause nerve injury at delivery, followed by a glenohumeral joint deformity because of the fragility without fixation in the thorax. [ABSTRACT FROM AUTHOR]

Fetal brain development is a complex, rapid, and multi-dimensional process that can be documented with MRI. In the second and third trimesters, there are predictable developmental changes that must be recognized and differentiated from disease. This review delves into the key biological processes that drive fetal brain development, highlights normal developmental anatomy, and provides a framework to identify pathology. We will summarize the development of the cerebral hemispheres, sulci and gyri, extra-axial and ventricular cerebrospinal fluid, and corpus callosum and illustrate the most common abnormal findings in the clinical setting. [ABSTRACT FROM AUTHOR]

Objectives and importance: Maternal and family patterns are changing, and these changes can influence birthweight. Past research and organisational reports focus on short temporal timelines or broad trends, but trends across a longer temporal period are important. The aim of this study is to assess the trends in birthweight and maternal characteristics across a 19-year period using descriptive statistics. Study type and methods: Birth records (n = 1,166,055) were obtained for a 19-year period (2000–2019) and a descriptive secular trend analysis was performed. Results and conclusions: Mean birthweight trended down across the study period, while rates of large for gestational age births increased. This appears to be driven by a decrease in gestational age across the period. Maternal factors, such as smoking, BMI and Indigenous status, were found to be linked with changes in mean birthweight and the proportion of small for gestational age or large for gestational age. More babies were born to older women by the end of the study period. There was a sharp rise in gestational diabetes, and more large for gestational age births to these women. Over time, the large for gestational age births started to decline, suggesting better care practices for women with gestational diabetes. [ABSTRACT FROM AUTHOR]

In the United States the rate of stillbirth after 28 weeks' gestation (late stillbirth) is 2.7/1000 births. Fetuses that are small for gestational age (SGA) or large for gestational age (LGA) are at increased risk of stillbirth. SGA and LGA are often categorized as growth or birthweight ≤ 10th and ≥ 90th centile, respectively; however, these cut-offs are arbitrary. We sought to characterize the relationship between birthweight and stillbirth risk in greater detail. Data on singleton births between 28- and 44-weeks' gestation from 2014 to 2015 were extracted from the US Centers for Disease Control and Prevention live birth and fetal death files. Growth was assessed using customized birthweight centiles (Gestation Related Optimal Weight; GROW). The analyses included logistic regression using SGA/LGA categories and a generalized additive model (GAM) using birthweight centile as a continuous exposure. Although the SGA and LGA categories identified infants at risk of stillbirth, categorical models provided poor fits to the data within the high-risk bins, and in particular markedly underestimated the risk for the extreme centiles. For example, for fetuses in the lowest GROW centile, the observed rate was 39.8/1000 births compared with a predicted rate of 11.7/1000 from the category-based analysis. In contrast, the model-predicted risk from the GAM tracked closely with the observed risk, with the GAM providing an accurate characterization of stillbirth risk across the entire birthweight continuum. This study provides stillbirth risk estimates for each GROW centile, which clinicians can use in conjunction with other clinical details to guide obstetric management. [ABSTRACT FROM AUTHOR]

Coenzyme Q10 (CoQ10) is a natural component widely present in the inner membrane of mitochondria. CoQ10 functions as a key cofactor for adenosine triphosphate (ATP) production and exhibits antioxidant properties in vivo. Mitochondria, as the energy supply center of cells, play a crucial role in germ cell maturation and embryonic development, a complicated process of cell division and cellular differentiation that transforms from a single cell (zygote) to a multicellular organism (fetus). Here, we discuss the effects of CoQ10 on oocyte maturation and the important role of CoQ10 in the growth of various organs during different stages of fetal development. These allowed us to gain a deeper understanding of the pathophysiology of embryonic development and the potential role of CoQ10 in improving fertility quality. They also provide a reference for further developing its application in clinical treatments. [ABSTRACT FROM AUTHOR]

During the early stages of the development of the living multiorgan systems, genome modifications other than sequence variation occur that guide cell differentiation and organogenesis. These modifications are known to operate as a fetal programming code during this period, and recent research indicates that there are some tissue-specific codes in organogenesis whose effects may persist after birth until adulthood. Consequently, the events that disrupt the pre-established epigenetic pattern could induce shifts in organ physiology, with implications on health from birth or later in adult life. Chronic kidney disease (CKD) is one of the main causes of mortality worldwide; its etiology is multifactorial, but diabetes, obesity, and hypertension are the main causes of CKD in adults, although there are other risk factors that are mainly associated with an individual's lifestyle. Recent studies suggest that fetal reprogramming in the developing kidney could be implicated in the susceptibility to kidney disease in both childhood and adulthood. Some epigenetic modifications, such as genome methylation status, dysregulation of miRNA, and histone coding alterations in genes related to the regulation of the renin-angiotensin axis, a common denominator in CKD, may have originated during fetal development. This review focuses on epigenetic changes during nephrogenesis and their repercussions on kidney health and disease. In addition, the focus is on the influence of environmental factors during pregnancy, such as maternal metabolic diseases and dietary and metabolic conditions, as well as some sex differences in fetal kidney reprogramming during which dysregulation of the renin-angiotensin system is involved. [ABSTRACT FROM AUTHOR]

Trophoblast cell syncytialization is essential for placental and fetal development. Abnormal trophoblast cell fusion leads to pregnancy pathologies, such as preeclampsia (PE), intrauterine growth restriction (IUGR), and miscarriage. 27-hydroxycholesterol (27-OHC) is the most abundant oxysterol in human peripheral blood synthesized by sterol 27-hydroxylase (CYP27A1) and is considered a critical mediator between hypercholesterolemia and a variety of related disorders. Gestational hypercholesterolemia was associated with spontaneous preterm delivery and low birth weight (LBW) in term infants, yet the mechanism is unclear. In this study, two trophoblast cell models and CD-1 mice were used to evaluate the effects of 27-OHC on trophoblast fusion during placenta development. Two different kinds of trophoblast cells received a dosage of 2.5, 5, or 10 uM 27-OHC. Three groups of pregnant mice were randomly assigned: control, full treatment (E0.5-E17.5), or late treatment (E13.5-E17.5). All mice received daily intraperitoneal injections of saline (control group) and 27-OHC (treatment group; 5.5 mg/kg). In vitro experiments, we found that 27-OHC inhibited trophoblast cell fusion in primary human trophoblasts (PHT) and forskolin (FSK)-induced BeWo cells. 27-OHC up-regulated the expression of the PI3K/AKT/mTOR signaling pathway-related proteins. Moreover, the PI3K inhibitor LY294002 rescued the inhibitory effect of 27-OHC. Inhibition of trophoblast cell fusion by 27-OHC was also observed in CD-1 mice. Furthermore, fetal weight and placental efficiency decreased and fetal blood vessel development was inhibited in pregnant mice treated with 27-OHC. This study was the first to prove that 27-OHC inhibits trophoblast cell fusion by Activating PI3K/AKT/mTOR signaling pathway. This study reveals a novel mechanism by which dyslipidemia during pregnancy results in adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To develop a deep-learning method for whole-body fetal segmentation based on MRI; to assess the method's repeatability, reproducibility, and accuracy; to create an MRI-based normal fetal weight growth chart; and to assess the sensitivity to detect fetuses with growth restriction (FGR). Methods: Retrospective data of 348 fetuses with gestational age (GA) of 19–39 weeks were included: 249 normal appropriate for GA (AGA), 19 FGR, and 80 Other (having various imaging abnormalities). A fetal whole-body segmentation model with a quality estimation module was developed and evaluated in 169 cases. The method was evaluated for its repeatability (repeated scans within the same scanner, n = 22), reproducibility (different scanners, n = 6), and accuracy (compared with birth weight, n = 7). A normal MRI-based growth chart was derived. Results: The method achieved a Dice = 0.973, absolute volume difference ratio (VDR) = 1.8% and VDR mean difference = 0.75% ( CI 95 % : − 3.95%, 5.46), and high agreement with the gold standard. The method achieved a repeatability coefficient = 4.01%, ICC = 0.99, high reproducibility with a mean difference = 2.21% ( CI 95 % : − 1.92%, 6.35%), and high accuracy with a mean difference between estimated fetal weight (EFW) and birth weight of − 0.39% ( CI 95 % : − 8.23%, 7.45%). A normal growth chart (n = 246) was consistent with four ultrasound charts. EFW based on MRI correctly predicted birth-weight percentiles for all 18 fetuses ≤ 10thpercentile and for 14 out of 17 FGR fetuses below the 3rd percentile. Six fetuses referred to MRI as AGA were found to be < 3rd percentile. Conclusions: The proposed method for automatic MRI-based EFW demonstrated high performance and sensitivity to identify FGR fetuses. Clinical relevance statement: Results from this study support the use of the automatic fetal weight estimation method based on MRI for the assessment of fetal development and to detect fetuses at risk for growth restriction. Key Points: • An AI-based segmentation method with a quality assessment module for fetal weight estimation based on MRI was developed, achieving high repeatability, reproducibility, and accuracy. • An MRI-based fetal weight growth chart constructed from a large cohort of normal and appropriate gestational-age fetuses is proposed. • The method showed a high sensitivity for the diagnosis of small fetuses suspected of growth restriction. [ABSTRACT FROM AUTHOR]

Fetal sex has been associated with different development trajectories that cause structural and functional differences between the sexes throughout gestation. Fetal magnetocardiography (fMCG) recordings from 123 participants (64 females and 59 males; one recording/participant) from a database consisting of low-risk pregnant women were analyzed to explore and compare fetal development trajectories of both sexes. The gestational age of the recordings ranged from 28 to 38 weeks. Linear metrics in both the time and frequency domains were applied to study fetal heart rate variability (fHRV) measures that reveal the dynamics of short- and long-term variability. Rates of linear change with GA in these metrics were analyzed using general linear model regressions with assessments for significantly different variances and GA regression slopes between the sexes. The fetal sexes were well balanced for GA and sleep state. None of the fHRV measures analyzed exhibited significant variance heterogeneity between the sexes, and none of them exhibited a significant sex-by-GA interaction. The absence of a statistically significant sex-by-GA interaction on all parameters resulted in none of the regression slope estimates being significantly different between the sexes. With high-precision fMCG recordings, we were able to explore the variation in fHRV parameters as it relates to fetal sex. The fMCG-based fHRV parameters did not show any significant difference in rates of change with gestational age between sexes. This study provides a framework for understanding normal development of the fetal autonomic nervous system, especially in the context of fetal sex. [ABSTRACT FROM AUTHOR]

Objectives: To determine the difference in time to attainment of full enteral feeds between fetal growth restricted (FGR) preterm neonates with and without absent/reversed end-diastolic flow (AREDF). Secondary objectives were to compare the short-term outcomes including the incidence of necrotizing enterocolitis (NEC) and feed intolerance between the two groups and to determine the factors affecting the time to attainment of full enteral feeds (FEF) among preterm FGR neonates. Methods: A prospective cohort study was conducted among consecutive preterm FGR neonates delivered at 28–36 weeks gestation admitted in level III NICU. An umbilical artery doppler ultrasound was performed antenatally for all participants to detect AREDF. FGR neonates with AREDF were taken as the study group and those without AREDF were taken as the comparison group. Time to attain FEF was defined as time taken to establish enteral feeds of 150 ml/kg/day and tolerating it for the next 3 consecutive days. Delayed attainment of FEF was taken as ≥10 days needed to attain FEF. Result: The median (IQR) time to attainment of full feeds was longer among neonates with AREDF compared to those without AREDF [12 (8, 16.5) vs 8 (5, 10) days; P < 0.001]. Neonates with AREDF had more feed intolerance [RR, 95% CI = 1.51 (1.13–2.02); P = 0.004], higher mortality [RR, 95% CI = 2.5 (1.02–6.2); P = 0.036], prolonged time to regain birth weight [15 (11.5, 19) days, P = 0.035], longer NICU stay [10 (7, 15), P < 0.001] and longer hospital stay [33 (23, 49), P < 0.001]. Also, neonates with AREDF had more hypoglycemia [RR, 95% CI=2.15 (1.2–3.7); P = 0.004], hypoxic ischemic encephalopathy [RR, 95% CI 5.05 (1.13–22.4); P = 0.016], hypothyroidism [RR, 95% CI= 8.08 (1.02–63.4), P = 0.016], cholestasis (P = 0.007), prolonged parenteral nutrition requirement [10 (7, 15) days, P < 0.001] and oxygen requirement [4.5 (2, 8) days, P < 0.001]. Multivariable logistic regression showed, AREDF [aOR 95% CI 2.91 (1.49–5.68), P = 0.002], lower gestational age [aOR 95% CI 0.724 (0.604–0.867), P < 0.001] and thrombocytopenia at birth [aOR 95% CI 2.625 (1.342–5.136), P = 0.005] are significant predictors of delayed attainment of full feeds among preterm FGR neonates. Conclusion: Preterm FGR neonates with AREDF are slower to attain FEF, have more feed intolerance, higher mortality, need longer time to regain birth weight, prolonged NICU stay and hospital stay. AREDF, lower gestation, sepsis and thrombocytopenia at birth are significant predictors of delayed full feed attainment among preterm FGR neonates. It is essential to devise strategies to reduce morbidity and mortality among this group of preterm neonates. [ABSTRACT FROM AUTHOR]

Amniotic fluid derived mesenchymal stem cells (AFMSCs), shed along the fetal development, exhibit superior multipotency and immunomodulatory properties compared to MSCs derived from other somatic tissues (e.g., bone marrow and fat). However, AFMSCs display heterogeneity due to source ambiguity, making them an underutilized stem cells source for translational clinical trials. Consequently, there is an urgent need to identify a method to purify the AFMSCs for clinical use. We found that the AFMSCs can be categorized into three distinct groups: kidney-specific AFMSCs (AFMSCs-K), lung-specific AFMSCs (AFMSCs-L), and AFMSCs with an undefined tissue source (AFMSCs-X). This classification was based on tissue-specific gene expression pattern of single cell colony. Additionally, we observed that AFMSCs-X, a minority population within the AFMSCs, exhibited the highest multipotency, proliferation, resistance to senescence and immuno-modulation. Our results showed that AFMSCs-X significantly improved survival rates and reduced bacterial colony forming units (CFU) in cecal ligation and puncture (CLP)-induced septic mice. Therefore, our study introduces a novel classification method to enhance the consistency and efficacy of AFMSCs. These subpopulations, originating from different tissue source, may offer a valuable and innovative resource of cells for regenerative medicine purposes. [ABSTRACT FROM AUTHOR]

Objective: Many cultures use herbal medicines in pregnancy as a safer treatment than traditional medicine to promote the mother and/or baby health. Horse chestnut, a medicinal herb that mainly contains aescin, is used for its vagotonic impact, vascular protection, and antiedematous properties. This research sought to assess the impact of prenatal administration of horse chestnut extract on fetal development of rats, which is a novel achievement in teratogenesis studies. Methods: Pregnant rats were allocated randomly into four groups. Horse chestnut extract was administered through oral gavage to the animals from day 0 to day 16 of pregnancy at doses of 10, 20, and 40 mg/kg. On day 18, after the cesarean process, the effects of the extract were estimated by morphological, skeletal, and histological studies. Results: Administration of the extract resulted in a substantial decrease in weight, head diameter, tail diameter, and crown-rump length of fetuses. There were no malformations and no lack of toes and legs, and all internal organs of the fetus were completely formed. Also, there was no difference in the overall skeletal opacity and density between the control and treatment groups. Moreover, heart cells and neurons were seen in all the groups but the formation of the central vein, portal area, and hepatic sinusoids were not observed in groups that received the extract. Conclusion: The result of this study revealed that oral administration of horse chestnut extract in pregnant rats could cause teratogenicity. However, some additional clinical studies may be necessary but according to our data, consumption of this herbal extract during pregnancy is not recommended. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) has conventionally been defined as any degree of glucose intolerance with onset or first recognition during pregnancy (Hinkle et al. in Sci Rep 8:12249, 2018). GDM has both short-term as well as long-term adverse materno-fetal consequences and increases the risk of future non-communicable diseases (NCDs), including type-2 diabetes. Probable epigenetic changes in children exposed to hyperglycemia in-utero predispose them to an increased risk for developing insulin resistance, obesity, type-2 diabetes, and associated NCDs in later life. Therefore, early detection and optimum management of GDM can go a long way in combating this rising epidemic of NCDs. It is pertinent to screen all pregnant women for glucose intolerance in pregnancy with the simple, economical and reliable single step test recommended by DIPSI and approved by the Ministry of Health & Family Welfare Government of India. An optimized strategy to achieve euglycemia can prevent the epidemic of NCD. Gestational programming is a distinctive process. The adverse stimuli (like hyperglycemia) or stresses that occur at critical or sensitive periods of fetal development ultimately lead to permanent changes in the structure, physiology, and metabolism of the growing fetus. This, in turn, predisposes these babies to increased NCD risk in their adult life — the famous J Endocrinol 2004;181:11–23 (Piper et al., 2004). [ABSTRACT FROM AUTHOR]

The placenta serves as an essential organ for fetal growth throughout pregnancy. Histone modification is a crucial regulatory mechanism involved in numerous biological processes and development. Nevertheless, there remains a significant gap in our understanding regarding the epigenetic regulations that influence trophoblast lineage differentiation, a fundamental aspect of placental development. Here, through comprehensive mapping of H3K4me3, H3K27me3, H3K9me3, and H3K27ac loci during the differentiation of trophoblast stem cells (TSCs) into syncytiotrophoblasts (STs) and extravillous trophoblasts (EVTs), we reveal dynamic reconfiguration in H3K4me3 and H3K27ac patterns that establish an epigenetic landscape conducive to proper trophoblast lineage differentiation. We observe that broad H3K4me3 domains are associated with trophoblast lineage-specific gene expression. Unlike embryonic stem cells, TSCs lack robust bivalent domains. Notably, the repression of ST- and EVT-active genes in TSCs is primarily attributed to the weak H3K4me3 signal rather than bivalent domains. We also unveil the inactivation of TSC enhancers precedes the activation of ST enhancers during ST formation. Our results provide a comprehensive global map of diverse histone modifications, elucidating the dynamic histone modifications during trophoblast lineage differentiation. [ABSTRACT FROM AUTHOR]

Aim of work: To determine the relationship between the gestational age and the (PSV, RI and PI) of the ductus arteriosus and lung maturity and to determine the effect of pregnancy-induced hypertension on these parameters. Material and methods: A prospective cohort study was carried out, in which 90 pregnant women at gestational age 34–40 weeks were selected, 50 as a control and 40 with pregnancy-induced hypertension (PIH). They underwent measurement of ductus arteriosus (DA) (PSV, RI and PI) and observing the percentage of the development of neonatal RDS in control and PIH cases. Results: There was a direct correlation between the PSV, PI, RI of ductus arteriosus and development of neonatal RDS. A cutoff value for GA, PSV, RI and PI for prediction of the subsequent development of RDS was determined in control ((35.7, 89.9, 0.80, 2.14), with sensitivity (71.4, 100, 85.7, 85.7%) and specificity (93, 97.7, 97.7, 93%), respectively), and PIH (35.7, 91.1, 0.80, 2.14), with sensitivity (71.4, 100, 85.7, 100%) and specificity (71.7, 100, 85.7, 100%), respectively). Conclusions: We concluded from our study that for the detection of fetal lung maturity in fetuses of GA from 34 to 40 weeks, it is better to combine GA, PSV, RI and PI of DA to detect lung maturity in control and PIH groups to get more accurate results. [ABSTRACT FROM AUTHOR]

Prenatal manganese (Mn) exposure may be related to poor birth outcomes; however, there are few relevant epidemiological reports on the effects of intrauterine Mn levels on intrauterine fetal and early childhood growth. From 2013 to 2016, 2082 pairs of mothers and infants were recruited in Wuhan, China, who provided an entire set of urine samples during their first, second, and third trimesters. Fetal head circumference (HC), abdominal circumference (AC), femoral length (FL), and estimated fetal weight (EFW) were obtained by ultrasound at the 16, 24, and 31 weeks of pregnancy. When the children were born, 6 months old, 12 months old, and 24 months old, their weight, height, weight-for-height, and BMI were measured. We used generalized linear models, generalized estimated equations, and restricted cubic spline curves (RCS) to investigate the linear and nonlinear relationships between antenatal Mn levels and fetal and early childhood growth. In all fetuses, Mn exposure during the 1st and 2nd gestation was associated with decreased fetal AC, FL, and EFW at 24 weeks (e.g., for each doubling of urinary Mn concentrations during the 1st and 2nd gestation, the SD score of EFW at 24 weeks decreased by − 4.16% (95% CI, − 6.22%, − 2.10%) and − 3.78% (95% CI, − 5.86%, − 1.70%)). Mn concentrations in the highest tertile group of the 1st and 2nd gestation were related to decreased fetus growth parameters compared to the lowest tertile group. For each doubling of the average Mn concentrations during pregnancy, the z-scores of weight, weight-for-height, and BMI at 12 months decreased, with percentage changes of − 2.93% (95% CI, − 5.08%, − 0.79%), − 3.25% (95% CI, − 5.56%, − 0.94%), and − 3.09% (95% CI, − 5.44%, − 0.73%). In the RCS model, we found a reverse U-shaped association between 1st trimester Mn concentration and fetal FL at 16 weeks and HC at 31 weeks in male fetuses and a non-linear association between mean Mn concentration during pregnancy and girls' weight-for-height and BMI at 6 months. Intrauterine exposure to Mn may be related to restricted growth in the fetus and early childhood, especially in fetuses at 24 weeks of gestation and children at 12 months of age. Also, meaningful curvilinear relationships were found in the sex stratification. [ABSTRACT FROM AUTHOR]

Epidemiological studies have robustly linked lower birth weight to later-life disease risks. These observations may reflect the adverse impact of intrauterine growth restriction on a child's health. However, causal evidence supporting such a mechanism in humans is largely lacking. Using Mendelian Randomization and 36,211 genotyped mother-child pairs from the FinnGen study, we assessed the relationship between intrauterine growth and five common health outcomes (coronary heart disease (CHD), hypertension, statin use, type 2 diabetes and cancer). We proxied intrauterine growth with polygenic scores for maternal effects on birth weight and took into account the transmission of genetic variants between a mother and a child in the analyses. We find limited evidence for contribution of normal variation in maternally influenced intrauterine growth on later-life disease. Instead, we find support for genetic pleiotropy in the fetal genome linking birth weight to CHD and hypertension. Our study illustrates the opportunities that data from genotyped parent-child pairs from a population-based biobank provides for addressing causality of maternal influences. A Mendelian Randomization study with 36,211 mother-child pairs indicates that maternal genetic variants, influencing a child's birth weight, impact the child's risk for common diseases through inheritance and not by effects on intrauterine growth. [ABSTRACT FROM AUTHOR]